UM  > 中華醫藥研究院
Potent Protection Against MPP+ -Induced Neurotoxicity via Activating Transcription Factor MEF2D by a Novel Derivative of Naturally Occurring Danshensu/Tetramethylpyrazine
Shengquan Hu1; Liang Wang2,3; Shinghung Mak2,4; Zaijun Zhang1; Daping Xu2,4; Haitao Li3; Yide Li2; Yuanjia Hu3; Simon Ming Yuen Lee3; Yuqiang Wang1; Yifan Han2,4
2016-12
Source PublicationNEUROMOLECULAR MEDICINE
ISSN1535-1084
Volume18Issue:4Pages:561-572
Abstract

Danshensu (DSS) and tetramethylpyrazine (TMP) are active ingredients of Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort that are widely used in oriental medicine. Structural combination of compounds with known biological activity may lead to the formation of a molecule with multiple properties or new function profile. In the current study, the neuroprotective effects of DT-010, a novel analogue in which TMP was coupled to DSS through an ester bond and two allyl groups at the carboxyl group, were evaluated in a cellular model of Parkinson’s disease (PD). As evidenced by the increase in cell survival, as well as the decrease in the number of Hoechst-stained apoptotic nuclei and the level of intracellular accumulation of reactive oxygen species, DT-010 at 3–30 µM substantially protected against MPP+-induced neurotoxicity in both PC12 cells and primary cerebellar granule neurons, a protection that was more potent and efficacious than its parent molecules DSS and TMP. Very encouragingly, we found that DT-010, but not DSS or TMP, could enhance myocyte enhancer factor 2D (MEF2D) transcriptional activity using luciferase reporter gene assay. The neuroprotective effects of DT-010 could be blocked by pharmacologic inhibition of PI3K pathways with LY294002, or MEF2D pathway with short hairpin RNA-mediated knockdown of MEF2D. Furthermore, western blot analysis revealed that DT-010 potentiates Akt protein expression against MPP+ to down-regulate MEF2D inhibitor GSK3β. Taken together, the results suggest that DT-010 prevents MPP+-induced neurotoxicity via enhancing MEF2D through the activation of PI3K/Akt/GSK3β pathway. DT-010 may be a potential candidate for further preclinical study for preventing and treating PD.

KeywordParkinson’s Disease Mef2d Neuroprotection Mpp++ Gsk3β Danshensu/tetramethylpyrazine Derivative
DOI10.1007/s12017-016-8399-5
Indexed BySCI
Language英语
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000387852200004
Fulltext Access
Citation statistics
Cited Times [WOS]:4   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy, Guangzhou, China
2.Department of Applied Biology and Chemical Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University, Hong Kong, China
3.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
4.The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China
Recommended Citation
GB/T 7714
Shengquan Hu,Liang Wang,Shinghung Mak,et al. Potent Protection Against MPP+ -Induced Neurotoxicity via Activating Transcription Factor MEF2D by a Novel Derivative of Naturally Occurring Danshensu/Tetramethylpyrazine[J]. NEUROMOLECULAR MEDICINE,2016,18(4):561-572.
APA Shengquan Hu.,Liang Wang.,Shinghung Mak.,Zaijun Zhang.,Daping Xu.,...&Yifan Han.(2016).Potent Protection Against MPP+ -Induced Neurotoxicity via Activating Transcription Factor MEF2D by a Novel Derivative of Naturally Occurring Danshensu/Tetramethylpyrazine.NEUROMOLECULAR MEDICINE,18(4),561-572.
MLA Shengquan Hu,et al."Potent Protection Against MPP+ -Induced Neurotoxicity via Activating Transcription Factor MEF2D by a Novel Derivative of Naturally Occurring Danshensu/Tetramethylpyrazine".NEUROMOLECULAR MEDICINE 18.4(2016):561-572.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Shengquan Hu]'s Articles
[Liang Wang]'s Articles
[Shinghung Mak]'s Articles
Baidu academic
Similar articles in Baidu academic
[Shengquan Hu]'s Articles
[Liang Wang]'s Articles
[Shinghung Mak]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Shengquan Hu]'s Articles
[Liang Wang]'s Articles
[Shinghung Mak]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.